Adolescence is a period of rapid neurobiological development and structural reorganization. This phase of development is a time of critical risk for the onset of psychiatric disturbances, perhaps most importantly for schizophrenia. The aim of this revised K23 CDA is to enhance the developing research skills of the PI, with the goal of making him an independent investigator devoted to studying adolescents prodromal for schizophrenia. The PI will receive intensive training in advanced neuroimaging techniques, adolescent development as well as in the neurobiology of schizophrenia and of its prodrome. Under the mentorship of Dr. Peterson, the PI will also train in the design, conduct and statistical modeling of longitudinal imaging studies of high-risk populations and in the safety and ethics of conducting research with adolescents. The PI plans to conduct mentored research with the goal of identifying the anatomical changes of cortical surface and cortical mantle during normal adolescent development and during the time when the symptoms of schizophrenia begin. The study will compare 65 adolescents or young adults deemed at "ultra-high risk" for developing psychosis (prodromals) - with 40 healthy adolescent controls. Imaging data will be collected twice, at a two-year time interval. Using sophisticated computational techniques for the analysis of the cortical surface and thickness, we will compare morphological features of the cortex in the controls with either (1) prodromal participants who do not develop psychosis ("non-converters") or (2) prodromal participants who do develop psychosis ("converters"). We will also correlate these morphological features with clinical symptoms and neuropsychological performance. We hypothesize that when compared to non- converters and controls, converters will exhibit baseline abnormalities in the prefrontal cortex and the anterior cingulate gyrus and, longitudinally, a more rapid loss of gray matter. By identifying anatomical biomarkers of risk for psychosis, which are not yet available, we may be able to predict more reliably who will develop schizophrenia and could possibly benefit from preventative treatments. This project is relevant to the mission of this agency, being one of the areas of "increased research emphasis" for NIMH. PUBLIC HEALTH RELEVANCE: Our ability to predict who will develop schizophrenia is currently limited. We aim to understand the brain changes that occur in those years before the illness strikes, with the hope that we will understand better its causes and that we may identify early those adolescents and young adults who are at greatest risk for developing schizophrenia and who may benefit from early treatment.